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Modulation of Type I Interferon System by African Swine Fever Virus
Elisabetta Razzuoli1, Giulia Franzoni2, Tania Carta2,3
1Department of Genoa, Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle D'Aosta, 16129 Genova, Italy.
Abstract:
African Swine Fever Virus (ASFV) has tropism for macrophages, which seems to play a crucial role in disease pathogenesis and viral dissemination. Previous studies showed that ASFV developed mechanisms to evade type I interferon (IFN) responses. Hence, we analyzed the ability of ASFV strains of diverse virulence to modulate IFN-β and IFN-α responses. Porcine monocyte-derived macrophages un-activated (moMΦ) or activated with IFN-α (moMΦ + FN-α) were infected with virulent (22653/14) or attenuated (NH/P68) ASFV strains, and expressions of IFN-β and of 17 IFN-α subtypes genes were monitored over time. ASFV strains of diverse virulence induced different panels of IFN genes: infection of moMΦ with either strains caused statistically significant up-regulation of IFN-α3, -α7/11, whereas only attenuated NH/P68 determined statistically significant up-regulation of IFN-α10, -α12, -α13, -α15, -α17, and IFN-β. Infection of activated moMΦ with either strains resulted in up-regulation of IFN-β and many IFN-α subtypes, but statistical significance was found only for IFN-α1, -α10, -α15, -α16, -α17 in response to NH/P68-infection only. These data revealed differences in type I IFNs expression patterns, with differences between strains of diverse virulence. In addition, virulent 22653/14 ASFV seems to have developed mechanisms to suppress the induction of several type I IFN genes.
Insights
African Swine Fever Virus (ASFV) virulence impacts the immune response. Different ASFV strains differentially modulate type I interferon (IFN) gene expression in macrophages, with virulent strains suppressing key IFN genes.
Area of Science:
- Veterinary Virology
- Immunology
- Molecular Biology
Background:
- African Swine Fever Virus (ASFV) targets macrophages, crucial for pathogenesis and spread.
- ASFV is known to possess mechanisms to evade host type I interferon (IFN) responses.
- Understanding ASFV's interaction with IFN is vital for disease control.
Purpose of the Study:
- To investigate how ASFV strains of varying virulence modulate type I IFN-β and IFN-α responses.
- To compare the immune evasion strategies of virulent versus attenuated ASFV strains.
Main Methods:
- Porcine monocyte-derived macrophages (moMΦ), both un-activated and IFN-α activated, were infected with virulent (22653/14) and attenuated (NH/P68) ASFV strains.
- Gene expression of IFN-β and 17 IFN-α subtypes was monitored over time post-infection.
Main Results:
- Both ASFV strains upregulated IFN-α3 and IFN-α7/11 in un-activated macrophages.
- Attenuated NH/P68 significantly upregulated additional IFN-α subtypes and IFN-β compared to virulent 22653/14.
- In activated macrophages, NH/P68 induced significant upregulation of specific IFN-α subtypes and IFN-β, while 22653/14 showed less significant induction.
Conclusions:
- ASFV strains of differing virulence exhibit distinct patterns of type I IFN gene modulation.
- Virulent ASFV strain 22653/14 appears to have evolved mechanisms to suppress the induction of multiple type I IFN genes.
- These findings highlight ASFV's complex strategies for evading innate immune responses.
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